切换至 "中华医学电子期刊资源库"
高级检索
中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2018, Vol. 07 ›› Issue (02) : 152 -155. doi: 10.3877/cma.j.issn.2095-3232.2018.02.016

所属专题： 文献；

基础研究

miR-17-5p通过靶向作用AKT3抑制肝癌侵袭和迁移
孔伟浩1, 李坤1, 肖翠翠1, 胡竞雄2, 黄泽楠3, 陈强星1, 张剑1,†()   
  1. 1. 510630　广州，中山大学附属第三医院肝移植科
    2. 510630　广州，中山大学附属第三医院肝胆外科
    3. 510630　广州，中山大学附属第三医院甲乳外科
  • 收稿日期:2018-01-18 出版日期:2018-04-10
  • 通信作者: 张剑
  • 基金资助:
    广东省科技计划项目(2014A020212159); 广州市科技计划项目(201707010112)

miR-17-5p inhibits invasion and metastasis of hepatocellular carcinoma through targeting effect on AKT3

Weihao Kong1, Kun Li1, Cuicui Xiao1, Jingxiong Hu2, Zenan Huang3, Qiangxing Chen1, Jian Zhang1,†()   

  1. 1. Department of Liver Transplantation, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    2. Department of Hepatobilliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    3. Department of Thyroid and Breast Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2018-01-18 Published:2018-04-10
  • Corresponding author: Jian Zhang
  • About author:
    Corresponding author: Zhang Jian, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

孔伟浩, 李坤, 肖翠翠, 胡竞雄, 黄泽楠, 陈强星, 张剑. miR-17-5p通过靶向作用AKT3抑制肝癌侵袭和迁移[J/OL]. 中华肝脏外科手术学电子杂志, 2018, 07(02): 152-155.

Weihao Kong, Kun Li, Cuicui Xiao, Jingxiong Hu, Zenan Huang, Qiangxing Chen, Jian Zhang. miR-17-5p inhibits invasion and metastasis of hepatocellular carcinoma through targeting effect on AKT3[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(02): 152-155.

目的

探讨microRNA（miR）-17-5p对肝细胞癌（肝癌）细胞侵袭和迁移的影响及机制。

方法

采用RT-PCR检测L-02人正常肝细胞及QGY-7703肝癌细胞中miR-17-5p的表达。miR-17-5p模拟物和模拟物对照分别转染QGY-7703肝癌细胞。Transwell和划痕试验检测miR-17-5p对肝癌细胞侵袭和迁移能力的影响。生物信息学分析确定miR-17-5p的靶基因，Western blot检测其在肝癌细胞中表达。对靶基因行siRNA沉默后，观察肝癌细胞的侵袭和迁移能力。两种细胞中microRNA比较采用t检验。

结果

miR-17-5p在肝癌细胞中表达量为0.16±0.04，较L-02正常肝细胞的1.01±0.19明显下调（t=-9.67，P<0.05）。转染miR-17-5p模拟物的肝癌细胞穿膜细胞数、迁移速度分别为（36±4）个、（5.37±0.15）mm/d，明显低于对照组的（62±7）个、（7.50±0.01）mm/d（t=-15.40，-32.00；P<0.05）。生物信息学分析显示AKT3是miR-17-5p的关键靶基因，AKT3在肝癌细胞中表达明显低于正常肝细胞。转染siRNA-AKT3的肝癌细胞穿膜细胞数、迁移速度分别为（13±3）个、（4.13±0.15）mm/d，明显低于对照组的（58±3）个、（7.23±0.25）mm/d（t=-17.88，-53.69；P<0.05）。

结论

miR-17-5p通过靶向作用于AKT3抑制肝癌细胞的侵袭和转移能力。

关键词: 癌，肝细胞, miR-17-5p, AKT3, 肿瘤侵润, 细胞迁移
Objective

To explore the effect and mechanism of microRNA (miR)-17-5p on the invasion and metastasis of hepatocellular carcinoma (HCC) cells.

Methods

Expression of miR-17-5p in the normal human L-02 hepatocyte and QGY-7703 HCC cells was detected by RT-PCR. QGY-7703 HCC cells were transfected by miR-17-5p mimic and mimic control respectively. Influence of miR-17-5p on the invasion and metastasis ability of HCC cells was detected using Transwell assay and scratch test. Target gene of miR-17-5p was confirmed by bioinformatic analysis, and its expression in HCC cells was detected by Western blot. After siRNA silenced by target gene, the invasion and metastasis ability of HCC cells were observed. Comparison of microRNA in the two kinds of cells was conducted by t test.

Results

Expression level of miR-17-5p in HCC cells was 0.16±0.04, significantly lower than 1.01±0.19 in normal L-02 hepatocytes (t=-9.67, P<0.05). Number of trans-membrane cells and metastasis rate of HCC cells transfected by miR-17-5p mimic were respectively 36±4 and (5.37±0.15) mm/d, significantly lower than 62±7 and (7.50±0.01) mm/d of control group (t=-15.40, -32.00; P<0.05). Bioinformatic analysis showed that AKT3 was the key target gene of miR-17-5p, and the expression of AKT3 in HCC cells was obviously higher than that of normal hepatocyte. Number of trans-membrane cells and metastasis rate of HCC cells transfected by siRNA-AKT3 were respectively 13±3 and (4.13±0.15) mm/d, significantly lower than 58±3 and (7.23±0.25) mm/d of control group (t=-17.88, -53.69; P<0.05).

Conclusion

miR-17-5p inhibits the invasion and metastasis ability of HCC cells through targeting effect on AKT3.

Key words: Carcinoma, hepatocellular, miR-17-5p, AKT3, Neoplasm invasiveness, Cell migration
图1 miR-17-5p靶基因生物信息学分析
图2 Western Blot检测AKT3在肝癌细胞中表达
[1]
Gerbes A, Zoulim F, Tilg H, et al. Gut roundtable meeting paper: selected recent advances in hepatocellular carcinoma[J]. Gut, 2018, 67(2):380-388.
[2]
Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov, 2017, 16(3):203-222.
[3]
Yang N, Ekanem NR, Sakyi CA, et al. Hepatocellular carcinoma and microRNA: new perspectives on therapeutics and diagnostics[J]. Adv Drug Deliv Rev, 2015(81):62-74.
[4]
Wang ZM, Wan XH, Sang GY, et al. miR-15a-5p suppresses endometrial cancer cell growth via Wnt/β-catenin signaling pathway by inhibiting WNT3A[J]. Eur Rev Med Pharmacol Sci, 2017, 21(21):4810-4818.
[5]
Feng ZY, Xu XH, Cen DZ, et al. miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1[J]. Eur Rev Med Pharmacol Sci, 2017, 21(21):4844-4852.
[6]
Gabra MM, Salmena L. microRNAs and acute myeloid leukemia chemoresistance:a mechanistic overview[J]. Front Oncol, 2017(7):255.
[7]
Yang Y, Hu Z, Zhou Y, et al. The clinical use of circulating microRNAs as non-invasive diagnostic biomarkers for lung cancers[J]. Oncotarget, 2017, 8(52):90197-90214.
[8]
Mjelle R, Sellaeg K, Saetrom P, et al. Identification of metastasis-associated microRNAs in serum from rectal cancer patients[J]. Oncotarget, 2017, 8(52):90077-90089.
[9]
Zhu WJ, Chen X, Wang YW, et al. MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway[J]. Oncotarget, 2017, 8(52):89631-89642.
[10]
Yokoi A, Yoshioka Y, Hirakawa A, et al. A combination of circulating miRNAs for the early detection of ovarian cancer[J]. Oncotarget, 2017, 8(52):89811-89823.
[11]
Bracken CP, Scott HS, Goodall GJ. A network-biology perspective of microRNA function and dysfunction in cancer[J]. Nat Rev Genet, 2016, 17(12):719-732.
[12]
Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease[J]. Cell, 2008, 133(2):217-222.
[13]
Olive V, Li Q, He L. mir-17-92:a polycistronic oncomir with pleiotropic functions[J]. Immunol Rev, 2013, 253(1):158-166.
[14]
Bobbili MR, Mader RM, Grillari J, et al. OncomiR-17-5p:alarm signal in cancer?[J]. Oncotarget, 2017, 8(41):71206-71222.
[15]
Liu F, Zhang F, Li X, et al. Prognostic role of miR-17-92 family in human cancers: evaluation of multiple prognostic outcomes[J]. Oncotarget, 2017, 8(40):69125-69138.
[16]
Fuziwara CS, Kimura ET. Insights into regulation of the miR-17-92 cluster of miRNAs in cancer[J]. Front Med, 2015(2):64.
[17]
Tan W, Li Y, Lim SG, et al. miR-106b-25/miR-17-92 clusters:polycistrons with oncogenic roles in hepatocellular carcinoma[J]. World J Gastroenterol, 2014, 20(20):5962-5972.
[18]
Concepcion CP, Bonetti C, Ventura A. The microRNA-17-92 family of microRNA clusters in development and disease[J]. Cancer J, 2012, 18(3):262-267.
[19]
Wang X, Liu S, Cao L, et al. miR-29a-3p suppresses cell proliferation and migration by downregulating IGF1R in hepatocellular carcinoma[J]. Oncotarget, 2017, 8(49):86592-86603.
[20]
Cui S, Sun Y, Liu Y, et al. MicroRNA-137 has a suppressive role in liver cancer via targeting EZH2[J]. Mol Med Rep, 2017, 16(16):9494-9502.
[21]
Li Y, Li Y, Chen Y, et al. MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis[J]. Cancer Cell Int, 2017(17):102.
[22]
Yang F, Yin Y, Wang F, et al. miR-17-5p promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat shock protein 27 pathway[J]. Hepatology, 2010, 51(5):1614-1623.
[23]
Liu D, Dong L, Liu Y, et al. A c-Myc/miR-17-5p feedback loop regulates metastasis and invasion of hepatocellular carcinoma[J]. Tumour Biol, 2016, 37(4):5039-5047.
[24]
Madhunapantula SV, Robertson GP. Targeting protein kinase-b3 (akt3) signaling in melanoma[J]. Expert Opin Ther Targets, 2017, 21(3):273-290.
[25]
Yang H, Zheng W, Shuai X, et al. MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma[J]. Oncotarget, 2015, 6(29):27736-27750.
[26]
Zhang Y, Huang W, Ran Y, et al. miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3[J]. Tumour Biol, 2015, 36(11):8309-8316.
[27]
Ma Y, She XG, Ming YZ, et al. MicroRNA-144 suppresses tumorigenesis of hepatocellular carcinoma by targeting AKT3[J]. Mol Med Rep, 2015, 11(2):1378-1383.
[1] 中国医师协会肝癌专业委员会. 肝细胞癌伴微血管侵犯诊断和治疗中国专家共识（2024版）[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 313-324.
[2] 李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[3] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[4] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[5] 公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[6] 李一帆, 朱帝文, 任伟新, 鲍应军, 顾俊鹏, 张海潇, 曹耿飞, 阿斯哈尔·哈斯木, 纪卫政. 血GP73水平在原发性肝癌TACE疗效评价中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 825-830.
[7] 刘敏思, 李荣, 李媚. 基于GGT与Plt比值的模型在HBV相关肝细胞癌诊断中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 831-835.
[8] 焦振东, 惠鹏, 金上博. 三维可视化结合ICG显像技术在腹腔镜肝切除术治疗复发性肝癌中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 859-864.
[9] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[10] 袁雨涵, 杨盛力. 体液和组织蛋白质组学分析在肝癌早期分子诊断中的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 883-888.
[11] 吴警, 吐尔洪江·吐逊, 温浩. 肝切除术前肝功能评估新进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 889-893.
[12] 邓万玉, 陈富, 许磊波. 肝硬化与非肝硬化乙肝相关性肝癌患者术后无复发生存比较及其影响因素分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 670-674.
[13] 王向前, 李清峰, 陈磊, 丘文丹, 姚志成, 李熠, 吴荣焕. 姜黄素抑制肝细胞癌索拉非尼耐药作用及其调控机制[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 729-735.
[14] 龚财芳, 赵俊宇, 游川. 围手术期肠内营养在肝癌肝切除患者中有效性及安全性的Meta分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 551-556.
[15] 张杰, 田广磊, 陈雄. 基于生物信息学分析探讨肝癌BRD4与预后关系及其ceRNA调控网络构建[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 568-576.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号